Peptide and protein delivery Flashcards
Compare and contrast differences between peptides &
protein therapeutics and small drug molecules
Molecular size: Peptides and proteins are generally much larger than small drug molecules. Peptides typically consist of fewer than 50 amino acids, while proteins can consist of hundreds or thousands of amino acids. Small drug molecules, on the other hand, usually have a molecular weight of less than 1000 Da.
Target specificity: Peptides and proteins tend to be highly specific in their interactions with targets, which can be advantageous for certain therapeutic applications. Small drug molecules, however, may have a broader range of targets, which can make them more effective against multiple diseases.
Mechanism of action: Peptides and proteins often work by binding to specific receptors or enzymes, which can have a direct effect on cellular signaling pathways. Small drug molecules may also work through binding to receptors or enzymes, but they can also act through other mechanisms, such as inhibiting specific metabolic pathways.
Delivery: Peptides and proteins are typically delivered through injection or infusion, as they may be degraded by digestive enzymes if taken orally. Small drug molecules, on the other hand, can be taken orally or administered through a variety of other routes.
Half-life: Peptides and proteins often have a short half-life in the body, meaning they are quickly broken down and eliminated. Small drug molecules can have longer half-lives, which can allow for less frequent dosing
Recognise common issues facing peptide & protein
formulation and delivery
Stability: Peptides and proteins are often prone to degradation by enzymes and other factors, such as heat and pH changes. This can impact their efficacy and shelf-life.
Immunogenicity: Because peptides and proteins are derived from biological sources, they can elicit an immune response in some patients. This can lead to adverse effects and limit their effectiveness.
Delivery: Peptides and proteins are typically administered via injection or infusion, as they may be degraded in the digestive tract. This can limit their patient acceptance and may require trained medical personnel to administer.
Solubility: Some peptides and proteins are poorly soluble in aqueous solutions, which can impact their bioavailability and efficacy.
Manufacturing: Peptides and proteins are often difficult to manufacture at scale, and the cost of production can be high. This can limit access to these therapeutics and impact their affordability.
Storage: Peptides and proteins may require specific storage conditions to maintain their stability, such as refrigeration or freezing. This can add to the cost and complexity of their distribution and administration.
Discuss common formulation strategies employed for
injectable peptide and protein medicines
Buffering: Adjusting the pH of the formulation can help to stabilize peptides and proteins and minimize their degradation. Common buffering agents include phosphate, acetate, and citrate.
Excipients: Excipients are non-active ingredients that are added to formulations to improve stability and efficacy. Examples include sugars, amino acids, surfactants, and polymers. Excipients can help to protect the protein from degradation, improve solubility, and enhance delivery.
Lyophilization: Also known as freeze-drying, lyophilization is a process that removes water from a formulation to improve its stability. This is often used for peptides and proteins that are sensitive to temperature or moisture. The lyophilized product can be reconstituted with a solvent prior to administration.
Microparticles and nanoparticles: Peptides and proteins can be encapsulated in microparticles or nanoparticles to improve their stability and control their release. These particles can protect the protein from degradation, enhance uptake by cells, and provide sustained release over time.
PEGylation: PEGylation involves attaching polyethylene glycol (PEG) to the protein, which can improve its pharmacokinetics and reduce its immunogenicity. PEGylation can increase the half-life of the protein, improve its solubility, and reduce its clearance by the body.
Co-formulation with other therapeutics: Peptides and proteins can be co-formulated with other drugs to enhance their efficacy or reduce their toxicity. For example, a protein drug could be co-formulated with a small molecule drug that enhances its uptake by cells.
Outline common strategies for non-invasive (mucosal)
delivery of peptide and protein therapeutics
Nanoparticles: Nanoparticles can be used to encapsulate peptides and proteins and protect them from degradation in the harsh environment of the mucosal membranes. Nanoparticles can also be functionalized to enhance their uptake by cells and to promote sustained release of the therapeutic.
Liposomes: Liposomes are spherical vesicles composed of lipid bilayers that can encapsulate hydrophilic and hydrophobic compounds, including peptides and proteins. Liposomes can protect the therapeutic from degradation and improve its uptake by cells in the mucosal membrane.
Mucoadhesive polymers: Mucoadhesive polymers can be used to increase the residence time of the therapeutic on the mucosal membrane, allowing for improved absorption. Examples of mucoadhesive polymers include chitosan and alginate.
Penetration enhancers: Penetration enhancers can be used to increase the permeability of the mucosal membrane and improve the absorption of the therapeutic. Examples of penetration enhancers include surfactants, bile salts, and fatty acids.
Prodrugs: Prodrugs are inactive derivatives of the therapeutic that are designed to be converted into the active form once inside the body. Prodrugs can be designed to improve the stability and bioavailability of the therapeutic, as well as its absorption across the mucosal membrane.
Self-emulsifying drug delivery systems (SEDDS): SEDDS are lipid-based formulations that can self-emulsify in the presence of water to form a microemulsion. SEDDS can be used to improve the solubility and bioavailability of poorly soluble peptides and proteins, as well as their absorption across the mucosal membrane.
